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Monthly vitamin D improves lumbar spine bone density in youth with HIV
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Monthly doses of vitamin D increased bone density in HIV-infected youth who were receiving Viread as part of their combination antiretroviral therapy, or cART, according to study results.
Peter L. Havens, MD, HIV program director at Children’s Hospital of Wisconsin, and colleagues compared the effects of a 50,000 IU dose of vitamin D3 taken every 4 weeks for 48 weeks against placebo in adolescent and young adult patients being chronically treated with Viread (tenofovir disoproxil fumarate [TDF], Gilead Sciences).
According to their results, vitamin D supplementation in these patients improved lumbar spine bone mineral density (LSBMD) within 24 weeks and continued through 48 weeks but not hip or total BMD.
TDF, which is widely used in cART and HIV pre-exposure prophylaxis, decreases BMD more than other nucleoside reverse transcriptase inhibitors, Havens and colleagues reported.
“We hypothesized that an ‘adolescent-friendly’ monthly dose of vitamin D3 ... would increase BMD and decrease PTH” — or parathyroid hormone, which is increased by TDF — “more effectively than a daily multivitamin containing vitamin D3 (400 IU) and calcium in youth with HIV being chronically treated with TDF-containing cART, independent of baseline vitamin D status,” they wrote in Clinical Infectious Diseases.
Between October 2012 and May 2016, Havens and colleagues enrolled 214 patients aged 16 to 24 years with behaviorally acquired HIV-1 infection being treated with TDF-containing cART for at least 180 days and with viral loads below 200 copies/mL within 90 days and at the time of screening. The study was conducted at six International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) sites in the United States and Puerto Rico.
They randomly assigned the patients to receive either vitamin D3 or placebo and gave participants in each group a multivitamin containing 400 IU of vitamin D3 and 162 mg of calcium to take each day. They collected urine and blood samples at baseline and weeks 12, 24 and 48 hours after a minimum 8-hour fast.
According to Havens and colleagues, multivitamin adherence was poor — just 49% between the two study groups — but treatment adherence was 100% in both groups. Among the participants who completed 48 weeks, LSBMD increased by 1.15% (95% CI, –0.75 to 2.74) in the group receiving monthly vitamin D3 (n = 99) and 0.09% (95% CI, –1.49 to 2.61; P = 0.25) in the placebo arm (n = 89).
“A strength of this study was enrollment of youth who had [a] viral load of less than 200 copies/mL for 180 days or more on unchanged cART, an index of good adherence to cART. A ‘youth-friendly’ dosing scheme with directly observed monthly vitamin D3/placebo administration was another key component of our study design,” Havens and colleagues wrote.
“The challenges of adherence with the daily multivitamin in our adolescent/young adult cohort suggest that the total vitamin D3 received dose would have been lower with daily dosing, even if a higher daily dose were used. We note that LSBMD was rising through 48 weeks. Longer follow-up perhaps could have shown a greater difference in BMD between the two treatment groups.” – by Gerard Gallagher
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Loss of bone mineral density in HIV-infected individuals is an ongoing problem that we do not have a good solution for yet. Both the HIV virus and some of the antiretroviral drugs — in particular, TDF — induce bone loss in this population. Efforts are being made to understand the underlying mechanisms and to find a lasting solution. I think this study is intriguing is because it involves a younger age group, individuals who are 16 to 24 years old. You want to protect their bones — they should actually be gaining bone rather than losing bone at this age. This is a period of life when bone is still growing, so you expect people to have an increase in their BMD. That there was no significant gain in BMD in the placebo group is concerning, and a gain in the intervention group is encouraging. The only challenge is that the gain was marginal — just 1.15% over a period of 48 weeks. It is very, very marginal. But if you look at it in the context of the fact that they did not lose bone density, that is probably encouraging.
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